We propose to use laboratory techniques to better understand the immunobiology of human immediate allergic reactions and to generate an improved approach to their therapy. The main tool in these studies is an in vitro model: antigenically induced histamine release from the isolated leukocytes of sensitive human donors. This system allows us to follow separately and precisely during treatment and/or the natural exposure to allergens the changes in (1) cell bound and serum reaginic (IgE) antibodies; (2) the changes in serum blocking (IgG) antibodies; and (3) the changes in the sensitivity of cells to antigen. We have demonstrated that the system itself reflects the patients clinical state and that (2) and (3) correlate, albeit weakly, with the clinical improvement which occurs in immunotherapy. We seek a better correlation and an understanding of the induced decrease in cellular reactivity as a means of improving immunotherapy. Associated with this is our aim to ascertain the clinical significance and utility of serologic measurements of the level of IgE and IgG antibody. In the context of this approach we plan a study of a new form of immunotherapy using "allergoids", allergens modified to decrease their allergenicity but maintaining their immunogenicity. It is hoped that these materials will simplify and improve the immunotherapy. We also plan to use the in vitro system to screen drugs with the aim of finding agents useful for the pharmacologic control of allergic disorders. Finally, we will continue our examination of the major allergens in materials of clinical importance and our efforts to provide standardization of the extracts currently used for diagnosis and therapy.